The basic chemical principles underlying the harmful effects of environmental agents are not fully understood. Our investigations on the molecular mechanisms of the biological effects of environental agents provide necessary basic information to fill the gaps in the present state of knowledge. The information obtained from these studies will allow more rapid and efficient design of ways to enhance the beneficial effects and minimize the health hazards of environmental agents. There are five projects included in this proposal. Their titles are: """"""""Oxidation of Biological Systems and Biomolecules"""""""", """"""""Dioxetane Chemiluminescence of Polyaromatic Hydrocarbon Metabolites in Microsomal Extracts and Whole Cells"""""""", """"""""Mode of Action of Water and Wastewater Disinfectants"""""""", """"""""Effects of Ultrasound on Nucleic Acids"""""""" and """"""""New Approaches to Singlet Oxygen for Biological Studies"""""""". These projects deal with wide range of agents and substrates, but the basic reactions are very similar - a direct or indirect reaction with nucleic acids that may result in mutagenesis or carcinogenesis. All five projects involve four stages of operation: 1) established procedures for the separation, isolation and characterization of major reaction products; 2) developing methods for the synthesis of the identified products in sufficient quantities for stages 3 and 4; 3) examining the apparent biological effects of each product in vitro and in vivo and 4) studying the molecular mechanisms of the biological phenomena. A project may emphasize any one of these stages, depending on the level of development that has been reached. The ultimate goal of all five projects is to reach a greater understanding of the molecular mechanisms responsible for the biological effects of environmental agents.
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